Increase In Spinal Excitability Research Articles

Location-specific cutaneous electrical stimulation of the footsole modulates corticospinal excitability to the plantarflexors and dorsiflexors during standing.

Non‐noxious electrical stimulation to distinct locations of the foot sole evokes location‐specific cutaneous reflex responses in lower limb muscles. These reflexes occur at latencies that may enable them to be mediated via a transcortical pathway. Corticospinal excitability to the plantarflexors and dorsiflexors was measured in 16 participants using motor evoked potentials (MEPs). Spinal excitability was measured in eight of the original participants using cervicomedullary motor evoked potentials (CMEPs). Measurements were collected with and without preceding cutaneous stimulus to either the heel (HEEL) or metatarsal (MET) locations of the foot sole, and evoked potentials were elicited to coincide with the arrival of the cutaneous volley at either the motor cortex or spinal cord. Plantarflexor MEPs and CMEPs were facilitated with cutaneous stimulation to the HEEL for MEPs (soleus p = 0.04, medial gastrocnemius (MG) p = 0.017) and CMEPs (soleus p = 0.047 and MG p = 0.015), but they were unchanged following MET stimulation for MEPs or CMEPs. Dorsiflexor MEPs were unchanged with cutaneous stimulation at either location, but dorsiflexor CMEPs increased with cutaneous stimulation (p = 0.05). In general, the increase in CMEP amplitudes was larger than the increase in MEP amplitudes, indicating that an increase in spinal excitability likely explains most of the increase in corticospinal excitability. The larger change observed in the CMEP also indicates that excitability from supraspinal sources likely decreased, which could be due to a net change in the excitability of intracortical circuits. This study provides evidence that cutaneous reflexes from foot sole skin are likely influenced by a transcortical pathway.

The Impact of Imperceptible Vibratory Noise on the Spinal Motor Reflex

Imperceptible noise stimulation has been shown to increase agility, stability and decrease muscle tremor. Previous research has shown that this effect is mediated via decreases in motor unit discharge variability and decreased motor unit synchronization. However, whether these motor unit effects arise from a spinal or cortical mechanisms is unknown and may change how these technologies are implemented to enhance human performance. PURPOSE: Determine the effect of imperceptible vibratory noise on the spinal motor reflex (Hoffman Reflex). METHODS: 12 males participated in the collection of a Hoffman reflex (H-reflex) recruitment curve and underwent either a randomized STIM (noise applied) trial or SHAM (control). The H-reflex recruitment curve was obtained from the median nerve of the subject’s dominant arm. The intensity that elicited the onset of the M-wave was used to standardize the H-reflex stimulation intensity. The STIM trial was performed by introducing a random imperceptible vibratory noise 3 seconds before the collection of the H-reflex. The test was repeated for a total of 10 stimulations with six seconds of rest between stimulations. The resulting H-reflex amplitudes were then normalized to the maximal M-wave (Mmax) found during the H-reflex recruitment curve. Data were assessed with a generalized estimating equation, clustering for multiple observations. RESULTS: The H-reflex was 19.1% (SE±2.42) of Mmax in the STIM trials and 17.4% (SE±2.66) in the SHAM trials, showing a significant increase of 1.73% with STIM (p = 0.0016). CONCLUSIONS: Subjects showed an increase in spinal excitability while undergoing STIM. The results demonstrate that the spinal reflex plays a role in the motor adaptation response to imperceptible vibration. This increase in spinal excitability suggests that the performance benefits of imperceptible noise stimulation may have a rapid onset, on the order of 10-20 milliseconds, in contrast to cortical mechanisms which are greater than 100 milliseconds. Determining which motor centers mediate the behavioral response to noise stimulation, and to what degree, will help define the optimal parameters for the application of noise stimulation.

Circadian variation of flexor withdrawal and crossed extensor reflexes in patients with restless legs syndrome.

An evening state of spinal hyperexcitability has been proposed to be a possible cause of evening increases in restless legs syndrome symptoms. Thus, the objective of the current study was to assess the circadian variation in spinal excitability in patients with restless legs syndrome based on flexor withdrawal reflex and crossed extensor reflex responses. The reflexes were elicited on 12 participants with restless legs syndrome and 12 healthy control participants in the evening (PM) and the morning (AM). Reflex response magnitudes were measured electromyographically and kinematically. Both the reflexes showed a circadian rhythm in participants with restless legs syndrome but not in control participants. Changes in ankle (median flexor withdrawal reflex PM: 16.0° versus AM: 2.8°, P=0.042; crossed extensor reflex PM: 0.8° versus AM: 0.2°, P=0.001) angle were significantly larger, and ankle angular velocity (median flexor withdrawal reflex PM: 38.8°s-1 versus AM: 13.9°s-1 , P=0.049; crossed extensor reflex PM: 2.4°s-1 versus AM: 0.5°s-1 , P=0.002) was significantly faster in the evening compared with the morning in participants with restless legs syndrome, for both reflexes. For participants with restless legs syndrome, evening change in hallux angle was significantly larger than morning responses (median PM: 5.0° versus AM: 1.3°, P=0.012). No significant differences for any of the electromyographic or kinematic variables were observed between participants with restless legs syndrome and controls. The flexor withdrawal reflex and the crossed extensor reflex show a circadian rhythm in participants with restless legs syndrome suggesting an evening increase in spinal excitability. We hypothesize the circadian variation in spinal excitability may be due to a possible nocturnal form of afferent circuitry central sensitization in the dorsal horn of the spinal cord in patients with restless legs syndrome.

Changes in spinal but not cortical excitability following combined electrical stimulation of the tibial nerve and voluntary plantar-flexion

Unilateral training involving voluntary contractions, neuromuscular electrical stimulation (NMES), or a combination of the two can increase the excitability of neural circuits bilaterally within the CNS. Many rehabilitation programs are designed to promote such "neuroplasticity" to improve voluntary movement following CNS damage. While much is known about this type of activity-dependent plasticity for the muscles that dorsi-flex the ankle, similar information is not available for the plantar-flexors. Presently, we assessed the excitability of corticospinal (CS) and spinal circuits for both soleus (SOL) muscles before and after voluntary contractions of the right plantar-flexors (VOL; 5 s on-5 s off, 40 min), NMES of the right tibial nerve (tnNMES; 5 s on-5 s off, 40 min), or both together (V + tnNMES). CS excitability for the right (rSOL) and left SOL (lSOL) muscles was assessed by quantifying motor evoked potentials elicited by transcranial magnetic stimulation. Spinal excitability was assessed using measures from the ascending limb of the M-wave versus H-reflex recruitment curve. CS excitability did not change for rSOL (the activated muscle) or lSOL following any condition. In contrast, there was a marked increase in spinal excitability for rSOL, but only following V + tnNMES; the slope of the M-wave versus H-reflex recruitment curve increased approximately twofold (pre = 7.9; post = 16.2) and H-reflexes collected when the M-wave was ~5 % of the maximal M-wave (M(max)) increased by ~1.5× (pre = 19 % M(max), post = 29 % M(max)). Spinal excitability for lSOL did not change following any condition. Thus, only voluntary contractions that were coupled with NMES increased CNS excitability, and this occurred only in the ipsilateral spinal circuitry. These results are in marked contrast to previous studies showing NMES-induced changes in CS excitability for every other muscle studied and suggest that the mechanisms that regulate activity-dependent neuroplasticity are different for SOL than other muscles. Further, while rehabilitation strategies involving voluntary training and/or NMES of the plantar-flexors may be beneficial for producing movement and reducing atrophy, a single session of low-intensity NMES and voluntary training may not be effective for strengthening CS pathways to the SOL muscle.

Autofluorescent Flavoprotein Imaging of Spinal Nociceptive Activity

Pain arises from activation of peripheral nociceptors, and strong noxious stimuli may cause an increase in spinal excitability called central sensitization, which is likely involved in many pathological pain states. So far, it has not been achieved to simultaneously visualize in vivo both the temporal and spatial aspects of spinal activity, including central sensitization. Using autofluorescent flavoprotein imaging (AFI), an optical technique suitable for mapping activity in nervous tissue, we demonstrate a close temporal and spatial correlation of electrically evoked nociceptive input with the spinal AFI signal, representing spinal neuronal activity. The AFI signal increases linearly with stimulation intensity. Furthermore, we found that the AFI signal was much larger in intensity and size when the same electrical stimulation was applied after the induction of central sensitization by a subcutaneous capsaicin injection. Finally, innocuous palpation of the hindpaw did not evoke an AFI response in naive animals, but after capsaicin injection a strong response was obtained. This is the first report demonstrating simultaneously the temporal and spatial propagation of spinal nociceptive activity in vivo.

Increased spinal excitability does not offset central activation failure

We hypothesized that if reduced spinal excitability contributes to central activation failure, then a caffeine-induced increase in spinal excitability would enhance postfatigue maximal voluntary activation and maximal voluntary contraction (MVC). Ten male volunteer subjects attended two laboratory sessions separated by at least 1 week. Contractile and electrical properties were assessed before, and 1 h after oral administration of caffeine (6 mg/kg) or placebo (all-purpose flour), and again following a fatigue protocol. The slope of the H reflex recruitment curve, normalized to that of the M wave (H(slp)/M(slp)), was used to estimate spinal excitability. Maximal voluntary activation was assessed using maximal EMG (EMG(max)) and twitch interpolation. Postfatigue, MVC torque declined (P<0.05) to 75.2+/-12.7 and 70.2+/-9.3% of the prefatigue values in the placebo (PL) and caffeine (CF) trials, respectively, and remained depressed throughout the recovery period. This was accompanied by a decline in % activation (P<0.05) from 99.6+/-0.3% (PL) and 99.8+/-0.3% (CF) to 94.8+/-3.5% (PL) and 95.3+/-5.0% (CF), indicating the presence of central activation failure. Caffeine offset the decline in H(slp)/M(slp )observed in the placebo trial (P<0.05), but it did not prevent the decline in maximal voluntary activation or MVC torque. Furthermore, although the decline in spinal excitability was correlated to the decline in EMG(max) (r=0.55, P<0.05) it was not correlated with the decline in % activation or MVC torque. Thus a fatigue-induced decline in spinal excitability did not limit maximal activation.

Modulation of spinal excitability during observation of bipedal locomotion

This study investigated whether a mirror mechanism exists for bipedal locomotion. We employed the soleus (plantar flexor) Hoffman reflex to investigate corticospinal excitability at the spinal level during observation of bipedal locomotion. The differential amplitude modulation of the left soleus Hoffman reflex during observation of bipedal heel-stepping (plantar dorsiflexion) (324+/-53 microV), standing still (383+/-60 microV), and bipedal toe-stepping (plantar flexion) (419+/-53 microV) reached significance (P < 0.05). The observation of bipedal toe-stepping produced a greater increase in spinal excitability than the observation of bipedal heel-stepping. These findings support the suggestion that there is a mirror mechanism for bipedal locomotion and they demonstrate that spinal excitability for observation of bipedal locomotion mirrors that for execution of bipedal locomotion.

Surround inhibition in human motor system

In sensory systems, a neural mechanism called surround inhibition (SI) sharpens sensation by creating an inhibitory zone around the central core of activation. In the motor system, the functional operation of SI remains to be demonstrated, although it has been hypothesized to contribute to the selection of voluntary movements. Here we test this hypothesis by using transcranial magnetic stimulation of the human motor cortex. The motor evoked potential of the little finger muscle is suppressed or unchanged during self-paced, voluntary movements of the index finger, mouth or leg, despite an increase in spinal excitability. This result indicates that motor excitability related to little finger movement is suppressed at the supraspinal level during these movements, and supports the idea that SI is an organizational principle of the motor system.

Effects of the capsaicin analogue resiniferatoxin on spinal nociceptive mechanisms in the rat: behavioral, electrophysiological and in situ hybridization studies

The effect of a single subcutaneous (s.c.) injection of the ultrapotent capsaicin analogue resiniferatoxin (RTX) on responses of adult rats to noxious thermal and mechanical stimulation was examined. The effects of RTX treatment on the nociceptive flexor reflex and activity-dependent increase in spinal excitability after conditioning C-fiber stimulation (CS) were also assessed. Finally, the expression of galanin message associated peptide (GMAP) mRNA in dorsal root ganglion (DRG) cells and the effects of the high affinity galanin receptor antagonist M35 on the flexor reflex in RTX-treated rats were evaluated. RTX, but not vehicle, produced marked thermal hypoalgesia on the hot plate test with partial recovery in about 50% of animals after about 2 weeks and no recovery in the remaining rats after 4 weeks. In all animals there was only a transient and moderate increase in paw withdrawal threshold to mechanical pressure. The flexor reflex in response to a C-fiber CS train was recorded 15–35 days after RTX or vehicle treatment. There was no difference between RTX and vehicle treated rats on baseline response, but RTX treatment lead to less wind-up during the CS and reduced hyperexcitability. This was particularly the case for rats which did not recover from RTX-induced hypoalgesia. The C-fiber mediated hyperexcitability was potentiated by the galanin receptor antagonist M35, more so in the non-recovered rats than in the partially recovered rats. The number of DRG cells expressing GMAP mRNA was significantly higher in non-recovered than in partially recovered rats. Thus, RTX produced marked and prolonged impairment of capsaicin-sensitive afferents and upregulation of the inhibitory neuropeptides GMAP and galanin in DRG neurons, which may underlie the prolonged effect of RTX.

Blockade of nitric oxide synthase differentially influences background activity and electrical excitability in rat dorsal horn neurones

A previous study has shown that inflammation of the gastrocnemius-soleus muscle in rats leads to an increase in excitability of dorsal horn neurones particularly in the spinal segment L3. Here, we have blocked the nitric oxide synthase (NOS) in L3 by spinal cord superfusion with N G-monomethyl- l-arginine ( l-NMMA) to find out if this effect is due to a release of nitric oxide (NO). l-NMMA had no influence on the excitability of L3 neurones but caused a marked increase in background activity. The l-NMMA effect on background activity was also present in rats with intact muscle. The data show that the myositis-induced increase in spinal excitability is not mediated by NO. The background activity, however, appears to be strongly dependent on NO production.